2ao0
From Proteopedia
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| - | [[Image:2ao0.gif|left|200px]] | + | [[Image:2ao0.gif|left|200px]] |
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| - | '''Structure of Aldehyde Reductase Holoenzyme in Complex with the Potent Aldose Reductase Inhibitor Fidarestat: Implications for Inhibitor Binding and Selectivity''' | + | {{Structure |
| + | |PDB= 2ao0 |SIZE=350|CAPTION= <scene name='initialview01'>2ao0</scene>, resolution 1.85Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene> and <scene name='pdbligand=FID:(2S,4S)-2-AMINOFORMYL-6-FLUORO-SPIRO[CHROMAN-4,4'-IMIDAZOLIDINE]-2',5'-DIONE'>FID</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Alcohol_dehydrogenase_(NADP(+)) Alcohol dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.2 1.1.1.2] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Structure of Aldehyde Reductase Holoenzyme in Complex with the Potent Aldose Reductase Inhibitor Fidarestat: Implications for Inhibitor Binding and Selectivity''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2AO0 is a [ | + | 2AO0 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AO0 OCA]. |
==Reference== | ==Reference== | ||
| - | Structure of aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity., El-Kabbani O, Carbone V, Darmanin C, Oka M, Mitschler A, Podjarny A, Schulze-Briese C, Chung RP, J Med Chem. 2005 Aug 25;48(17):5536-42. PMID:[http:// | + | Structure of aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity., El-Kabbani O, Carbone V, Darmanin C, Oka M, Mitschler A, Podjarny A, Schulze-Briese C, Chung RP, J Med Chem. 2005 Aug 25;48(17):5536-42. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16107153 16107153] |
[[Category: Alcohol dehydrogenase (NADP(+))]] | [[Category: Alcohol dehydrogenase (NADP(+))]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: tim barrel]] | [[Category: tim barrel]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:51:53 2008'' |
Revision as of 13:51, 20 March 2008
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| , resolution 1.85Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Activity: | Alcohol dehydrogenase (NADP(+)), with EC number 1.1.1.2 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of Aldehyde Reductase Holoenzyme in Complex with the Potent Aldose Reductase Inhibitor Fidarestat: Implications for Inhibitor Binding and Selectivity
Overview
Structure determination of porcine aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat was carried out to explain the difference in the potency of the inhibitor for aldose and aldehyde reductases. The hydrogen bonds between the active-site residues Tyr50, His113, and Trp114 and fidarestat are conserved in the two enzymes. In aldose reductase, Leu300 forms a hydrogen bond through its main-chain nitrogen atom with the exocyclic amide group of the inhibitor, which when replaced with a Pro in aldehyde reductase, cannot form a hydrogen bond, thus causing a loss in binding energy. Furthermore, in aldehyde reductase, the side chain of Trp220 occupies a disordered split conformation that is not observed in aldose reductase. Molecular modeling and inhibitory activity measurements suggest that the difference in the interaction between the side chain of Trp220 and fidarestat may contribute to the difference in the binding of the inhibitor to the enzymes.
About this Structure
2AO0 is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.
Reference
Structure of aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity., El-Kabbani O, Carbone V, Darmanin C, Oka M, Mitschler A, Podjarny A, Schulze-Briese C, Chung RP, J Med Chem. 2005 Aug 25;48(17):5536-42. PMID:16107153
Page seeded by OCA on Thu Mar 20 15:51:53 2008
